Triple A (Allgrove) syndrome: an unusual association with syringomyelia

Abstract

Triple A (Allgrove) syndrome was first described by Allgrove in 1978 in two pairs of siblings. Since then, about 100 cases have been reported, all of them displaying an autosomal recessive pattern of inheritance. Clinical picture is characterized by achalasia, alacrimia and ACTH-resistant adrenal failure. A progressive neurological syndrome including central, peripheral and autonomic nervous system impairment, and mild mental retardation is often associated. The triple A syndrome gene, designated AAAS, is localized on chromosome 12q13. It consists of 16 exons, encoding for a 546 aminoacid protein called ALADIN (Alacrimia-Achalasia-aDrenal Insufficiency Neurologic disorder).We report on a 13 year-old boy presenting with Addison’s disease, dysphagia, muscle weakness, excessive fatigue and recent onset gait ataxia. The analysis of the AAAS gene revealed a homozygous missense mutation in exon 12. It was a T > G transversion at nucleotide position 1224, resulting in a change of leucine at amino acid position 381 into arginine (Leu381Arg or L381R). Brain appearance was found normal at magnetic resonance imaging (MRI) and functional spectroscopy analysis showed normal levels of the main metabolites. Spine MRI showed a cystic cavity within the spinal cord (syringomyelia), localized between the sixth cervical vertebra and the first thoracic vertebra. Cerebellar tonsils descended 7 mm caudal to foramen magnum, consistently with a mild type 1 Chiari malformation. Mild posterior inter-vertebral disk protrusions were evident between T9 and T10 and between L4 and L5.To our knowledge, this is the first report describing type 1 Chiari malformation and multiple spinal cord abnormalities in a patient with Allgrove syndrome.

<p>Triple A syndrome (Allgrove syndrome): improving outcomes with a multidisciplinary approach</p>

“…3,50,51 In about one-third of patients, autonomic dysfunction symptoms include postural hypotension, abnormal cardiovascular responses and arrhythmias, anisocoria, abnormal pupillary reflexes, impaired or increased sweating, and impotence 6. While seizures have been described, those are hypoglycemic in origin 52. In a single case report, a patient with 3A syndrome was found to have Arnold Chiari malformation and syringomyelia, and Bizzari et al suggest screening diagnosed patients with magnetic resonance imaging of brain and spine, even without the presence of neurologic symptoms 52…”

“…While seizures have been described, those are hypoglycemic in origin 52. In a single case report, a patient with 3A syndrome was found to have Arnold Chiari malformation and syringomyelia, and Bizzari et al suggest screening diagnosed patients with magnetic resonance imaging of brain and spine, even without the presence of neurologic symptoms 52…”

AAA Syndrome, Case Report of a Rare Disease

“…Since the first reported case of AAA syndrome in 1978, over 100 cases presenting with the clinical features of esophageal achalasia, alacrimia, and adrenal insufficiency have been described. 19 Alacrimia was the first sign to become evident in our patients, probably, it was already present at birth, as parents noted lack of tears on crying. Recurrent vomiting, poor appetite and failure to thrive were present at two years of age.…”

Triple-A Syndrome (TAS): An In-Depth Overview on Genetic and Phenotype Heterogeneity

“…While the exact function of the ALADIN protein remains mostly unclear, attempts have been made to clarify the pathogenetic mechanism of the different mutations reported, seemingly causing impaired nuclear import of DNA repair proteins and the intensification of oxidative stress status in the cell. Figure 1) 3,9,41,[61][62][63][64][65][66][67][68][69]10,[70][71][72][73][74][75][76][77][78][79]11,[80][81][82][83][84][85][86][87][88][89]12,[90][91][92][93][94][95][96][97][98][99]16,[100][101]<...>…”